alpha-GalCer analog, 7DW8-5 – a potential adjuvant in Cancer Immunotherapy?

Alpha-Gal-Cer interactions with AP cells and its adjuvant effect

Alpha-Gal-Cer (KRN7000) adjuvant effect in innate and adaptive immunities via dendritic and NKT cells. Source: Alphagalcer.net.

Current cancer vaccine strategies strive to efficiently deliver in situ immunogenic Tumour-Associated Antigens (TAAs) into  functional Antigen-Presenting Cells (APCs).  Stimulated APCs cells then initiate anti-tumour reactions through local and complex immune interactions targeting also the tumour microenvironment.

In this context, Xu et al. have recently developed a new effective oral cancer vaccine platform presenting potent immunogenicity and anti-tumour activity with long-lasting protective memory response (1).

The authors have designed optimized Salmonella-based vectors (Salmonella SPI2-encoded T3SS system) co-administrated with a Natural Killer (NKT) cells ligand (2). The delivery of heterogeneous TAAs into APCs has been proven to display enhanced anti-tumour activity through bacterial expressed TAAs-specific immune reponses.

Chemically synthesized NKT cells ligands (alpha-Galactosylceramide known as the αGalCer KRN7000 or alpha-GalCer) and its superior binding affinity analog 7DW8-5 were already known to enhance the immunogenicity and anti-tumour efficacy of bacterial vaccine vectors (3, 4). α-Gal-Cer is known to exhibit potent antitumor activity in various murine experimental cancer models.

Xu et al. clearly show here the potential interest of 7DW8-5 as a vaccine adjuvant in clinical tumour treatment with oral vaccines.

Specific ligand for human and mouse natural killer T (NKT) cells. α-Gal-Cer (KRN7000) exhibits various immunological effects through NKT cell functions including potent antitumor effect.

α-Gal-Cer (KRN7000) specific ligand for natural killer T (NKT) cells.

Sources:

  1. Xu et al. “Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens” (2014) Cancer Res Published Online First September 11, 2014. DOI:10.1158/0008-5472.CAN-14-1169.
  2. Nicol A. et al. “Comparison of clinical and immunological effects of intravenous and intradermal administration of a-galactosylceramide (KRN7000)-pulsed dendritic cells” (2011) Clin Cancer Res, 1;17(15):5140-51. DOI: 10.1158/1078-0432.CCR-10-3105.
  3. Xiong G. et al. “Novel cancer vaccine based on genes of Salmonella pathogenicity island 2” (2010) Int J Cancer,126:2622-34. DOI: 10.1002/ijc.24957.
  4. Li X. et al. “Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant” (2010) Proc Natl Acad Sci U S A 2010;107:13010-5. DOI: 10.1073/pnas.1006662107.
Philippe Fixe, PhD
Written by Philippe Fixe, PhD
Philippe Fixe is Marketing Director at tebu-bio, passionate about innovation and R&D in Life sciences, Biotechnology, Medical research, Drug discovery, and also a keen photographer.